Ceftiofur, a semisynthetic cephalosporin, is a broad-spectrum antibiotic against both Gram-positive and Gram-negative bacteria including beta-lactamase-producing bacterial strains and anaerobes. Its antibacterial activity results from the inhibition of mucopeptide synthesis in the cell wall in a similar fashion to other cephalosporins. Ceftiofur is used in the treatment of respiratory infections in cattle and pigs. The chemical designation is 7-[[(2-amino-4-thiazolyl)(methoxyimino)acetyl]amino]-3-[[2-furanylcarbonyl)thio]methyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid. The sodium and hydrochloride salts are administered intramuscularly and intravenously.
Ceftiofur is first disclosed in U.S. Pat. No. 4,464,367, which also discloses a process for preparing Ceftiofur and its sodium salt.
U.S. Pat. No. 4,902,683 claims crystalline hydrochloride salt of Ceftiofur. According to this patent the conventional free acid and its sodium salt are unstable and are obtained as amorphous in nature.
U.S. Pat. No. 5,721,359 claims crystalline Ceftiofur free acid and process for the preparation of same.
U.S. Pat. No. 4,937,330 claims a process for the preparation of Ceftiofur sodium. Though this patent mentioned the Ceftiofur sodium obtained as crystal form, this patent does not provide the X-ray diffraction pattern of the said crystal. According to this patent Ceftiofur sodium is isolated from aqueous tetrahydrofuran as a unique solid phase characterized by birefringent lath- and rod-shaped particles. Moreover further treatment with a dry, organic solvent (e.g., acetone or ethanol) produces solvent-free amorphous Ceftiofur sodium upon drying.
Hence all the prior art literature reported so far provide amorphous Ceftiofur sodium, and owing to the amorphous nature, the conventional Ceftiofur sodium is less stable. Further, owing to the amorphous nature, purification is very difficult, and hence not preferable in large scale preparation.
In our PCT publication WO 2007/042917 (Indian Application No. 1462/CHE/2005) a novel polymorph of crystalline Ceftiofur Sodium having moisture content in the range of 7.0 to 11.0% is provided and is named as Form D.
In our continued research we have identified novel anhydrous crystalline form of Ceftiofur sodium, which is having good stability over conventional amorphous product. None of the prior art suggests or even motivates the present invention.